ISSN / EISSN : 2589-5370 / 2589-5370
Published by: Elsevier BV (10.1016)
Total articles ≅ 1,224
Latest articles in this journal
eClinicalMedicine, Volume 44; https://doi.org/10.1016/j.eclinm.2022.101283
Summary Background Anemia is the most frequent hematologic abnormality among people living with human immunodeficiency virus (HIV) (PLWHIV) and is associated with HIV disease progression and higher risk of mortality of the patients. However, there is a wide variation of the prevalence of anemia among PLWHIV in different clinical settings. We aimed to obtain more precise estimates of prevalence of anemia and severity of anemia among PLWHIV, which may be important for patients, caregivers, researchers and health policy-makers. Methods We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library for original articles reporting the prevalence of anemia defined using age and sex-specific hemoglobin levels according to World Health Organization criteria among PLWHIV from inception to August 31, 2021. We used DerSimonian-Laird random-effects meta-analyses to obtain pooled prevalence and 95% confidence intervals (CIs) of anemia and severity of anemia among PLWHIV. A univariable meta-regression has been conducted to assess the association between anemia prevalence and study characteristics, including study design, median year of sampling, geographical region, World Bank Income level, and proportion of antiretroviral therapy (ART). Findings We included 63 observational studies covering 110,113 PLWHIV. The pooled prevalence of anemia was 39.7% (95% CI: 31.4%-48.0%) for children living with HIV aged <15 years, 46.6% (95% CI: 41.9%-51.4%) for adults (men and non-pregnant women) living with HIV aged ≥15 years, and 48.6% (95% CI: 41.6%-55.6%) for pregnant women living with HIV. Among adults living with HIV, the pooled prevalence of severity of anemia was 21.6% (95% CI: 19.9%-23.3%), 22.6% (95% CI: 14.8%-30.4%), and 6.2% (95% CI: 4.4%-8.1%) for mild, moderate and severe anemia, respectively. Compared with East Africa, anemia prevalence among adults living with HIV was higher in Southern Africa (p = 0.033). Interpretation Anemia is prevalent among PLWHIV. Thus, policies, strategies, and programs should be considered to identify the predictors of anemia among PLWHIV to reduce the burden of anemia among patients in the ART era.
eClinicalMedicine, Volume 44; https://doi.org/10.1016/j.eclinm.2022.101274
Summary Background It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke. Methods We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression. Findings Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (p<0.001/<0.001) by 7 days, shifted the modified Rankin Scale to a worse outcome by day 90, adjusted common odds ratio (OR) 1.46 (95% CI 1.01–2.11), and was associated with an increased death rate by day 90 (hazard ratio 2.17, 95% CI 1.24–3.79). Other outcomes (disability - Barthel Index, quality of life - EQ-visual analogue scale, cognition - telephone mini-mental state examination, and mood - Zung depression scale) were also worse with continuing treatment. Interpretation In this pre-specified subgroup analysis of the large ENOS trial, continuing prior antihypertensive therapy within 12 h of stroke onset in a predominantly ischaemic stroke population was unsafe with worse functional outcome, disability, cognition, mood, quality of life and increased death. Future studies assessing continuing or stopping prior antihypertensives in the context of thrombectomy are awaited.
eClinicalMedicine, Volume 44; https://doi.org/10.1016/j.eclinm.2022.101271
Summary Background Non-invasive pneumococcal pneumonia causes significant morbidity and mortality in older adults. Understanding pneumococcal sero-epidemiology in adults ≥50 years is necessary to inform vaccination policies and the updating of pneumococcal vaccines. Methods We conducted a systematic review and random-effects meta-analysis to determine the proportion of community-acquired pneumonia (CAP) in people ≥50 years due to pneumococcus and the proportion caused by pneumococcal vaccine serotypes. We searched MEDLINE, EMBASE and PubMed from 1 January 1990 to 30 March 2021. Heterogeneity was explored by subgroup analysis according to a) patient group (stratified versus age) and depth of testing, b) detection/serotyping method, and c) continent. The protocol is registered with PROSPERO (CRD42020192002). Findings Twenty-eight studies were included (34,216 patients). In the period 1–5 years after introduction of childhood PCV10/13 immunisation, 18% of CAP cases (95% CI 13–24%) were attributable to pneumococcus, with 49% (43–54%) of pneumococcal CAP due to PCV13 serotypes. The estimated proportion of pneumococcal CAP was highest in one study that used 24-valent serotype-specific urinary-antigen detection (ss-UAD)(30% [28–31%]), followed by studies based on diagnostic serology (28% [24–33%]), PCR (26% [15–37%]), ss-UAD14 (17% [13–22%]), and culture alone (14% [10–19%]). A higher estimate was observed in Europe (26% [21–30%] than North America (11% [9–12%](p<0·001). PCV13-serotype estimates were also influenced by serotyping methods. Interpretation Non-invasive pneumococcal CAP and vaccine-type pneumococcal CAP remains a burden in older adults despite widespread introduction of pneumococcal infant immunisation. Studies heavily reliant on ss-UADs restricted to vaccine-type serotypes may overestimate the proportion of potentially vaccine-preventable pneumococcal pneumonia. Sero-epidemiological data from low-income countries are lacking.
eClinicalMedicine, Volume 44; https://doi.org/10.1016/j.eclinm.2022.101276
Summary Heatstroke is increasingly becoming a significant concern due to global warming. Systemic inflammation and coagulopathy are the two major factors that provoke life-threatening organ dysfunction in heatstroke. Dysregulated thermo-control induces cellular injury, damage-associated molecular patterns release, hyperinflammation, and hypercoagulation with suppressed fibrinolysis to produce heatstroke-induced coagulopathy (HSIC). HSIC can progress to disseminated intravascular coagulation and multiorgan failure if severe enough. Platelet count, D-dimer, soluble thrombomodulin, and inflammation biomarkers such as interleukin-6 and histone H3 are promising markers for HSIC. In exertional heatstroke, the measurement of myoglobin is helpful to anticipate renal dysfunction. However, the optimal cutoff for each biomarker has not been determined. Except for initial cooling and hydration, effective therapy continues to be explored, and the use of antiinflammatory and anticoagulant therapies is under investigation. Despite the rapidly increasing risk, our knowledge is limited, and further study is warranted. In this review, we examine current information and what future efforts are needed to better understand and manage HSIC.
eClinicalMedicine, Volume 44; https://doi.org/10.1016/j.eclinm.2021.101268
Summary Background Hearing loss affects over 50% of people in the US across their lifespan and there is a lack of decision modeling frameworks to inform optimal hearing healthcare delivery. Our objective was to develop and validate a microsimulation model of hearing loss across the lifespan in the US. Methods We collaborated with the Lancet Commission on Hearing Loss to outline model structure, identify input data sources, and calibrate/validate DeciBHAL-US (Decision model of the Burden of Hearing loss Across the Lifespan). We populated the model with literature-based estimates and validated the conceptual model with key informants. We validated key model endpoints to the published literature, including: 1) natural history of sensorineural hearing loss (SNHL), 2) natural history of conductive hearing loss (CHL), and 3) the hearing loss cascade of care. We reported the coefficient of variance root mean square error (CV-RMSE), considering values ≤15% to indicate adequate fit. Findings For SNHL prevalence, the CV-RMSE for model projected male and female age-specific prevalence compared to sex-adjusted National Health and Nutrition Examination Survey (NHANES) data was 4.9 and 5.7%, respectively. Incorporating literature-based age-related decline in SNHL, we validated mean four-frequency average hearing loss in the better ear (dB) among all persons to longitudinal data (CV-RMSE=11.3%). We validated the age-stratified prevalence of CHL to adjusted NHANES data (CV-RMSE=10.9%). We incorporated age- and severity-stratified time to first hearing aid (HA) use data and HA discontinuation data (adjusted for time-period of use) and validated to NHANES estimates on the prevalence of adult HA use (CV-RMSE=10.3%). Interpretation Our results indicate adequate model fit to internal and external validation data. Future incorporation of cost and severity-stratified utility data will allow for cost-effectiveness analysis of US hearing healthcare interventions across the lifespan. Further research might expand the modeling framework to international settings. Funding This study was funded by the National Institute on Deafness and Other Communication Disorders and the National Institute on Aging (3UL1-TR002553–03S3 and F30 DC019846).
eClinicalMedicine, Volume 44; https://doi.org/10.1016/j.eclinm.2021.101266
Summary Background People who experience incarceration die by suicide at a higher rate than those who have no prior criminal justice system contact, but little is known about the effectiveness of interventions in other criminal justice settings. We aimed to synthesise evidence regarding the effectiveness of interventions to reduce suicide and suicide-related behaviours among people in contact with the criminal justice system. Methods We searched Embase, PsycINFO, MEDLINE, and grey literature databases for articles published between 1 January 2000 and 1 June 2021. The protocol was registered with PROSPERO (CRD42020185989). Findings Thirty-eight studies (36 primary research articles, two grey literature reports) met our inclusion criteria, 23 of which were conducted in adult custodial settings in high-income, Western countries. Four studies were randomised controlled trials. Two-thirds of studies (n=26, 68%) were assessed as medium quality, 11 (29%) were assessed as high quality, and one (3%) was assessed as low quality. Most had considerable methodological limitations and very few interventions had been rigorously evaluated; as such, drawing robust conclusions about the efficacy of interventions was difficult. Interpretation More high-quality evidence from criminal justice settings other than adult prisons, particularly from low- and middle-income countries, should be considered a priority for future research. Funding This work was funded by the Australian government's National Suicide Prevention Taskforce. RB is supported by a National Health and Medical Research Council (NHMRC) Emerging Leader Investigator Grant (EL2; GNT2008073). MW is supported by a NHMRC Postgraduate Scholarship (GNT1151103). SF was funded by the NIHR HTA Programme (HTA Project:16/159/09).
eClinicalMedicine, Volume 43; https://doi.org/10.1016/j.eclinm.2021.101249
Summary Background Congenital heart disease (CHD) is the leading cause of morbidity and mortality from birth defects worldwide. We report an overview of trends in CHD mortality in 204 countries and territories over the past 30 years and associations with age, period, and birth cohort. Methods Cause-specific CHD mortality estimates were derived from the Global Burden of Disease 2019 study. We utilised an age-period-cohort model to estimate overall annual percentage changes in mortality (net drifts), annual percentage changes from 0 to 4 to 65–69 years (local drifts), period and cohort relative risks (period/cohort effects) between 1990 and 2019. This approach allows for the examination and differentiation of age, period, and cohort effects in the mortality trends, with the potential to identify disparities and treatment gaps in cardiac care. Findings CHD is the leading cause of deaths from non-communicable diseases (NCDs) in those under 20 years. Global CHD deaths in 2019 were 217,000 (95% uncertainty interval 177,000–262,000). There were 129 countries with at least 50 deaths. India, China, Pakistan, and Nigeria had the highest mortality, accounting for 39.7% of deaths globally. Between 1990 and 2019, the net drift of CHD mortality ranged from –2.41% per year (95% confidence interval [CI] –2.55, –2.67) in high Socio-demographic Index (SDI) countries to –0.62% per year (95% CI: –0.82, –0.42) in low-SDI countries. Globally, there was an emerging transition in the age distribution of deaths from paediatric to adult populations, except for an increasing trend of mortality in those aged 10–34 years in Mexico and Pakistan. During the past 30 years, favourable mortality reductions were generally found in most high-SDI countries like South Korea (net drift = –4.0% [95% CI –4.8 to –3.1] per year) and the United States (–2.3% [–2.5 to –2.0]), and also in many middle-SDI countries like Brazil (–2.7% [–3.1 to 2.4]) and South Africa (–2.5% [–3.2 to –1.8]). However, 52 of 129 countries had either increasing trends (net drifts ≥0.0%) or stagnated reductions (≥–0.5%) in mortality. The relative risk of mortality generally showed improving trends over time and in successively younger birth cohorts amongst high- and high-middle-SDI countries, with the exceptions of Saudi Arabia and Kazakhstan. 14 middle-SDI countries such as Ecuador and Mexico, and 16 low-middle-SDI countries including India and 20 low-SDI countries including Pakistan, had unfavourable or worsening risks for recent periods and birth cohorts. Interpretation CHD mortality is a useful and accessible indicator of trends in the provision of congenital cardiac care both in early childhood and across later life. Improvements in the treatment of CHD should reduce the risk for successively younger cohorts and shift the risk for all age groups over time. Although there were gains in CHD mortality globally over the past three decades, unfavourable period and cohort effects were found in many countries, raising questions about adequacy of their health care for CHD patients across all age groups. These failings carry significant implications for the likelihood of achieving the Sustainable Development Goal targets for under-5 years and NCD mortality. Funding Supported by the National Natural Science Foundation of China (81525002, 31971048, 82073573 to ZZ and HZ), Shanghai Outstanding Medical Academic Leader program (2019LJ22 to HZ), and Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01 to HZ), the Bill & Melinda Gates Foundation for the Global Burden of Disease Project (to NJK) and NHMRC fellowship administered through the University of Melbourne (to GCP).
eClinicalMedicine, Volume 43; https://doi.org/10.1016/j.eclinm.2021.101161
Background Prostate-specific antigen (PSA) testing is limited in identifying prostate cancer (PCa) with modestly elevated PSA levels. Therefore, a robust method for the diagnosis of PCa is urgently needed. Methods A total of 203 men with a PSA level of ≥4 ng/ml were eligible for enrollment in this study from July 2018 to May 2021, and randomly divided into a training set (n=78) and a validation set (n=125). Circulating tumor cells (CTCs) were detected using telomerase-based CTC detection (TBCD), and the diagnostic ability was evaluated using receiver operating characteristic (ROC) and logistic regression analyses. Findings In the training set, the area under the curve (AUC) of CTCs was 0.842 with a sensitivity of 80.33% and specificity of 82.35%. In the validation set, the AUC of CTCs was 0.789, with a sensitivity of 79.31% and specificity of 81.58%. There was no significant difference between CTCs (AUC=0.793) and PSA (AUC=0.697) in the range of 4-50 ng/ml. In the ranges of 4-20 ng/ml and 4-10 ng/ml, the AUC of CTCs were 0.811 and 0.825, respectively, which were superior to the AUC of PSA (0.588 and 0.541). The sensitivity and specificity of CTCs in the three PSA groups were higher than 80%. Moreover, we further established a CTC+PSA combined model, which could significantly improve the diagnostic ability of a PSA level of ‘4-10 ng/ml'. Interpretation TBCD could be a valuable method for distinguishing PCa and benign prostatic disease, especially in the PSA diagnostic gray area of ‘4-10 ng/ml'.
eClinicalMedicine, Volume 44; https://doi.org/10.1016/j.eclinm.2021.101260
Summary Background Most claims-based frailty instruments have been designed for group stratification of older populations according to the risk of adverse health outcomes and not frailty itself. We aimed to develop and validate a tool based on one-year hospital discharge data for stratification on Fried's frailty phenotype (FP). Methods We used a three-stage development/validation approach. First, we created a clinical knowledge-driven electronic frailty score (eFS) calculated as the number of deficient organs/systems among 18 critical ones identified from the International Statistical Classification of Diseases and Related Problems, 10th Revision (ICD-10) diagnoses coded in the year before FP assessment. Second, for eFS development and internal validation, we linked individual records from the Lc65+ cohort database to inpatient discharge data from Lausanne University Hospital (CHUV) for the period 2004-2015. The development/internal validation sample included community-dwelling, non-institutionalised residents of Lausanne (Switzerland) recruited in the Lc65+ cohort in three waves (2004, 2009, and 2014), aged 65-70 years at enrolment, and hospitalised at the CHUV at least once in the year preceding the FP assessment. Using this sample, we selected the best performing model for predicting the dichotomised FP, with the eFS or ICD-10-based variables as predictors. Third, we conducted an external validation using 2016 Swiss nationwide hospital discharge data and compared the performance of the eFS model in predicting 13 adverse outcomes to three models relying on well-designed and validated claims-based scores (Claims-based Frailty Index, Hospital Frailty Risk Score, Dr Foster Global Frailty Score). Findings In the development/internal validation sample (n = 469), 14·3% of participants (n = 67) were frail. Among 34 models tested, the best-subsets logistic regression model with four predictors (age and sex at FP assessment, time since last hospital discharge, eFS) performed best in predicting the dichotomised FP (area under the curve=0·71; F1 score=0·39) and one-year adverse health outcomes. On the external validation sample (n = 54,815; 153 acute care hospitals), the eFS model demonstrated a similar performance to the three other claims-based scoring models. According to the eFS model, the external validation sample showed an estimated prevalence of 56·8% (n = 31,135) of frail older inpatients at admission. Interpretation The eFS model is an inexpensive, transportable and valid tool allowing reliable group stratification and individual prioritisation for comprehensive frailty assessment and may be applied to both hospitalised and community-dwelling older adults. Funding The study received no external funding.
eClinicalMedicine, Volume 44; https://doi.org/10.1016/j.eclinm.2021.101259
Summary Background Health care-associated infections (HCAI) in neonatal units in low- and middle-income countries (LMIC) are a major cause of mortality. This scoping review aimed to synthesise published literature on infection prevention and care bundles addressing neonatal HCAI in LMICs and to construct a Classification Framework for their components (elements). Methods Five electronic databases were searched between January 2001 and July 2020. A mixed-methods approach was applied: qualitative content analysis was used to build a classification framework to categorise bundle elements and the contents of the classification groups were then described quantitatively. Findings 3619 records were screened, with 44 eligible studies identified. The bundle element Classification Framework created involved: (1) Primary prevention, (2) Detection, (3) Case management, and Implementation (3 + I). The 44 studies included 56 care bundles with 295 elements that were then classified. Primary prevention elements (128, 43%) predominated of which 71 (55%) focused on central line catheters and mechanical ventilators. Only 12 elements (4%) were related to detection. A further 75 (25%) elements addressed case management and 66 (88%) of these aimed at outbreak control. Interpretation The 3 + I Classification Framework was a feasible approach to reporting and synthesising research for infection-relevant bundled interventions in neonatal units. A shift towards the use in infection prevention and care bundles of primary prevention elements focused on the neonate and on commonly used hospital devices in LMIC (e.g., self-inflating bags, suctioning equipment) would be valuable to reduce HCAI transmission. Detection elements were a major gap. Funding This work was made possible in part by the John D. and Catherine T. MacArthur Foundation, the Bill & Melinda Gates Foundation, ELMA Philanthropies, The Children's Investment Fund Foundation UK, The Lemelson Foundation, and the Ting Tsung and Wei Fong Chao Foundation under agreements to William Marsh Rice University. The project leading to these results has also received the support of a fellowship from the "la Caixa" Foundation (ID 100010434). The fellowship code is LCF/BQ/EU19/11710040. EJAF is an Academic Clinical Fellow whose salary is funded by the UK National Institute for Health Research (NIHR). NES receives a Research Training Program Scholarship (Australian Commonwealth Government).